Hypotensive effect of 13‐hydroxylinoleic acid in the rat: mediation via the release of a CGRP‐like mediator from capsaicin‐sensitive nerves

D van Heuven‐Nolsen, T Muis, F Engels… - British journal of …, 1995 - Wiley Online Library
D van Heuven‐Nolsen, T Muis, F Engels, PAJ Henricks, TL Buckley, FP Nijkamp
British journal of pharmacology, 1995Wiley Online Library
1 The effect of 13‐hydroxylinoleic acid (13‐HODE) on changes in blood pressure in the rat
was measured. 2 13‐HODE (0.1− 100 μg kg− 1) had no direct eifect on blood pressure in
the rat and had no eifect on histamine (0.1–1000 μg kg− 1‐induced changes in blood
pressure. In contrast, it was found that 13‐HODE itself induced a decrease in diastolic
arterial blood pressure when it was injected intravenously after either a single dose of
histamine (10, 100 or 1000 μg kg− 1) or after a dose‐response curve of histamine (0.1–1000 …
  • 1
    The effect of 13‐hydroxylinoleic acid (13‐HODE) on changes in blood pressure in the rat was measured.
  • 2
    13‐HODE (0.1 −100 μg kg−1) had no direct eifect on blood pressure in the rat and had no eifect on histamine (0.1–1000 μg kg−1‐induced changes in blood pressure. In contrast, it was found that 13‐HODE itself induced a decrease in diastolic arterial blood pressure when it was injected intravenously after either a single dose of histamine (10, 100 or 1000 μg kg−1) or after a dose‐response curve of histamine (0.1–1000 μg kg−1).
  • 3
    This hypotensive eifect of 13‐HODE was not observed after administration of the endothelium‐dependent vasodilator, acetylcholine (0.1–10 μg kg−1), the endothelium‐independent vasodilator, sodium nitroprusside (0.1–100 μg kg−1) or the inflammatory mediator, leukotriene B4 (0.1–300 μg kg−1). However, prior injection of bradykinin (0.1–100 μg kg−1) allowed a dose‐dependent hypotensive effect of 13‐HODE to be revealed.
  • 4
    The hypotensive effect of 13‐HODE after histamine and bradykinin could be inhibited by neonatal capsaicin treatment of the rats (50 mg kg−1, s.c. on day 1 and 2 after birth).
  • 5
    Ruthenium red (120 μg kg−1 min−1), an inhibitor of excitatory effects on sensory nerves, and the CGRP antagonist, CGRP8.37 (1–3 μg kg−1 min−1) also inhibited the hypotensive effect of 13‐HODE.
  • 6
    It is concluded that the hypotensive effect of 13‐HODE in the rat after histamine and bradykinin is due to the release of a CGRP‐like substance from sensory nerves. These results highlight the possibility that endogenous 13‐HODE could be involved in the neurogenic regulation of blood pressure.
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